Astellas menopause study meets endpoints but leukemia drug disappoints

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There was good and bad news this week from Japanese company Astellas Pharma Inc. as one of its trials yielded positive results, while another didn’t meet its endpoints.

Astellas Pharma announced pivotal phase 3 results for its study of fezolinetant, an investigational oral, nonhormonal compound being studied for the treatment of moderate to severe vasomotor symptoms (VMS) due to menopause.

The results were published in The Lancet.

The study met the four coprimary efficacy endpoints. Fezolinetant 30 and 45 mg once daily demonstrated statistically significant improvements from baseline in VMS frequency and severity at four and 12 weeks compared to placebo. These improvements were observed as early as week 1, and the effects were maintained throughout the remainder of the 52-week study period. 

During the double-blind period, treatment-emergent adverse events (TEAEs) occurred in 37% of fezolinetant 30 mg, 43% of 45 mg and 45% of placebo participants. The safety profile of fezolinetant observed during the 40-week extension period was consistent with that of the 12-week placebo-controlled period. Over the 52 weeks of the study, the most commonly reported TEAEs were headache and COVID-19

“The SKYLIGHT 1 study showed that women receiving fezolinetant experienced a reduction in the frequency and severity of VMS and improvements in quality of life over the one-year treatment period,” said Genevieve Neal-Perry, chair, UNC School of Medicine Department of Obstetrics and Gynecology. 

“As a healthcare provider, I truly understand the burden of VMS due to menopause on my own patients, and I’m really excited about this potential new nonhormonal treatment option to help women experiencing moderate to severe VMS.”

Astellas notes important report

The key secondary endpoint related to sleep disturbance. While improvements in sleep disturbance were observed, statistical significance was not met for either fezolinetant dose at 12 weeks. Additional sleep analyses showed a higher proportion of patients in the fezolinetant 30 and 45 mg groups reported improvements at four and 12 weeks compared with placebo. Further evidence was shown in a questionnaire, which demonstrated a significant and clinically meaningful improvement at four and 12 weeks that was maintained through 52 weeks.

“This publication of the SKYLIGHT 1 study is another important report of a phase 3 randomized trial assessing the utility of an investigational nonhormonal agent, fezolinetant, that targets the neurokinin 3 receptor to reduce the frequency and severity of moderate to severe VMS due to menopause, and we are honored to see it published in The Lancet,” said Ahsan Arozullah, senior vice president and head of development therapeutic areas, Astellas. 

“This manuscript, which provides further insights into the safety and effectiveness of fezolinetant, reinforces Astellas’ commitment to turning innovative science into value for patients.”

Fezolinetant is an investigational selective neurokinin 3 (NK3) receptor antagonist and is not approved for use anywhere in the world. Regulatory applications for fezolinetant are under review in the U.S., EU, Switzerlandand Australia. If approved, fezolinetant would be a first-in-class, nonhormonal treatment option to reduce the frequency and severity of moderate to severe VMS due to menopause.

Astellas leukemia drug fails to meet endpoint 

Astellas and the Blood and Marrow Transplant Clinical Trials Network (BMT CTN) announced topline results from their phase 3 clinical trial evaluating gilteritinib as a maintenance therapy following allogeneic hematopoietic stem cell transplantation (HSCT) for patients with FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutated acute myeloid leukemia (AML). 

Based on the data, the study did not meet its pre-defined primary endpoint of relapse-free survival (RFS) for patients treated with gilteritinib compared to placebo. 

“While we are disappointed by these results, we remain committed to providing AML patients with treatment options throughout the disease continuum,” Arozullah said. 

“We will be conducting a thorough review of the full data set and plan to share detailed results in the future.”

“Though the phase 3 MORPHO clinical trial did not meet its primary endpoint, we are proud of the fact that we were able to garner international cooperation to address this important question in a rare disease,” said Mary M. Horowitz, principal investigator of the BMT CTN Data and Coordination Center. 

“In collaboration with Astellas, we will continue the evaluation of the study results, which included multiple clinically meaningful secondary endpoints, and assess their impact on AML patient care.”

Gilteritinib is a FLT3 inhibitor with demonstrated activity against FLT3-ITD, a common driver mutation that presents with a high disease burden and poor prognosis, and FLT3-tyrosine kinase domain (TKD) mutations. It is available as XOSPATA in the U.S., Japan, China and selected European countries for the treatment of adult patients who have relapsed or refractory FLT3+ AML.

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